The term "microencapsulated product" as used in this specification is understood to mean a product, e.g. a microparticle or microcapsule, wherein a pharmaceutically active agent is dispersed within a polymeric matrix or is encapsulated by a polymer coating, wall or membrane. Microencapsulated products are known in the art and methods for forming said microencapsulated products may be based on emulsion technology.
Prior art processes employing emulsion-based technology may proceed by producing a water-in-oil emulsion (so-called primary emulsion) by dispersing a solution of active agent in a solution of matrix- or wall-forming polymer (Polymer) (the solvent for active agent and the solvent for the polymer (the polymer solvent) being immiscible). The primary emulsion is then dispersed in, e.g. an aqueous phase (so-called external phase) to form droplets (containing active agent-in polymer) dispersed in the external phase. The droplets so formed are then hardened by removing the polymer solvent from the droplets to form a microencapsulated product. Several methods for polymer solvent removal are known including distillation, evaporation under reduced pressure and/or heat or extracting the polymer solvent by partitioning the droplets in an extraction medium immiscible with the polymer solvent. A problem with all of these hardening steps is that they are slow and during polymer solvent removal the active agent may leach out of the droplets, resulting in poor encapsulation efficiency. By "encapsulation efficiency" is meant the measure of the amount of active substance incorporated into the microencapsulated product as a percentage of the total amount of active agent employed in a process.
In an attempt to accelerate the hardening step, it has been suggested to transfer the mixture containing the droplets to an extraction medium immediately after the mixture is formed thereby removing sufficient polymer solvent sufficiently quickly to enable the droplets to harden before a significant quantity of active agent can leach out of the droplets. Nevertheless, the need to transfer the mixture to the extraction medium immediately after the mixture is formed imposes a constraint on the process which may render it impractical and unreliable particularly when active agents are used which are highly soluble in an extraction medium.
There remains a need to provide a process of microencapsulation of an active agent to form a microencapsulated product which reliably incorporates an active agent in a polymer with high encapsulation efficiency.
Surprisingly the applicant has found that the mixture formed by mixing primary emulsion and an external phase may be dispersed to form a microencapsulated product, the microencapsulated product being formed without the need for a subsequent hardening step, i.e. a polymer solvent removal step.